AU2002246733B2 - Transgenic animals comprising a humanized immune system - Google Patents
Transgenic animals comprising a humanized immune system Download PDFInfo
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- AU2002246733B2 AU2002246733B2 AU2002246733A AU2002246733A AU2002246733B2 AU 2002246733 B2 AU2002246733 B2 AU 2002246733B2 AU 2002246733 A AU2002246733 A AU 2002246733A AU 2002246733 A AU2002246733 A AU 2002246733A AU 2002246733 B2 AU2002246733 B2 AU 2002246733B2
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- A—HUMAN NECESSITIES
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- A01K2267/035—Animal model for multifactorial diseases
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25659100P | 2000-12-19 | 2000-12-19 | |
| US60/256,591 | 2000-12-19 | ||
| PCT/US2001/049413 WO2002059263A2 (en) | 2000-12-19 | 2001-12-19 | Transgenic animals comprising a humanized immune system |
Publications (2)
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| AU2002246733A1 AU2002246733A1 (en) | 2003-02-06 |
| AU2002246733B2 true AU2002246733B2 (en) | 2007-09-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002246733A Expired AU2002246733B2 (en) | 2000-12-19 | 2001-12-19 | Transgenic animals comprising a humanized immune system |
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|---|---|
| US (1) | US20030093818A1 (ja) |
| EP (1) | EP1409646B1 (ja) |
| JP (2) | JP2005505236A (ja) |
| AU (1) | AU2002246733B2 (ja) |
| CA (1) | CA2432133C (ja) |
| DK (1) | DK1409646T3 (ja) |
| ES (1) | ES2389251T3 (ja) |
| WO (1) | WO2002059263A2 (ja) |
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| EP1476469B1 (en) | 2002-01-25 | 2015-11-18 | Novo Nordisk A/S | Monoclonal antibodies against extracellular loops of c5ar |
| JP5478003B2 (ja) * | 2003-07-10 | 2014-04-23 | アンスティチュ パストゥール | ヒトの主要組織適合複合体（ｍｈｃ）の表現型を有するトランスジェニックマウス、その実験のための使用および応用方法 |
| US7663017B2 (en) | 2003-07-30 | 2010-02-16 | Institut Pasteur | Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications |
| EP1701611B1 (en) * | 2003-12-24 | 2011-05-18 | G2 Inflammation Pty Ltd | Transgenic non-human mammal comprising a polynucleotide encoding human or humanized c5ar |
| CA2555185C (en) | 2004-02-06 | 2020-03-24 | Morphosys Ag | Anti-cd38 human antibodies and uses therefor |
| US7994298B2 (en) | 2004-09-24 | 2011-08-09 | Trustees Of Dartmouth College | Chimeric NK receptor and methods for treating cancer |
| US20090298195A1 (en) | 2005-01-05 | 2009-12-03 | F-Star Biotechnologische Forschungs-Und Entwicklun Gseges M.B.H. | Synthetic immunoglobulin domains with binding properties engineered in regions of the molecule different from the complementarity determining regions |
| RU2425841C2 (ru) | 2005-10-12 | 2011-08-10 | МорфоСис АГ | Получение и анализ полностью человеческих лечебных антител-производных hucal gold, специфичных к человеческому cd38 |
| AT503889B1 (de) | 2006-07-05 | 2011-12-15 | Star Biotechnologische Forschungs Und Entwicklungsges M B H F | Multivalente immunglobuline |
| AT503861B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von t-zell-rezeptoren |
| JP5162587B2 (ja) | 2006-08-22 | 2013-03-13 | ジーツー インフラメイション プロプライエタリー リミテッド | 改良された特性を持つ坑−Ｃ５ａＲ抗体 |
| US8921279B2 (en) | 2007-06-26 | 2014-12-30 | F-Star Biotechnologische Forschungs—und Entwicklungsges. m.b.H | Display of binding agents |
| BRPI0907532A2 (pt) | 2008-02-20 | 2015-07-28 | G2 Inflammation Pty Ltd | Anticorpos anti-c5ar humanizados |
| EP2113255A1 (en) | 2008-05-02 | 2009-11-04 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Cytotoxic immunoglobulin |
| US20090328240A1 (en) * | 2008-06-24 | 2009-12-31 | Sing George L | Genetically modified mice as predictors of immune response |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
| EP2564695B1 (en) * | 2009-07-08 | 2015-04-15 | Kymab Limited | Animal models and therapeutic molecules |
| WO2011059836A2 (en) | 2009-10-29 | 2011-05-19 | Trustees Of Dartmouth College | T cell receptor-deficient t cell compositions |
| US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
| DK2718322T3 (en) | 2011-06-06 | 2018-12-03 | Novo Nordisk As | THERAPEUTIC ANTIBODIES |
| WO2013033626A2 (en) | 2011-08-31 | 2013-03-07 | Trustees Of Dartmouth College | Nkp30 receptor targeted therapeutics |
| CN106995822B (zh) | 2011-09-19 | 2021-06-29 | 科马布有限公司 | 定制供人类使用的抗体、可变结构域和链 |
| EP2761008A1 (en) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| ES2651517T3 (es) | 2011-10-28 | 2018-01-26 | Regeneron Pharmaceuticals, Inc. | Ratones con complejo mayor de histocompatibilidad modificado genéticamente |
| RS57893B1 (sr) * | 2011-10-28 | 2019-01-31 | Regeneron Pharma | Miševi sa genetski modifikovanim receptorom t ćelija |
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| EP4052572A1 (en) | 2011-10-28 | 2022-09-07 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules |
| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| CN104395344B (zh) | 2012-05-07 | 2019-08-13 | 达特茅斯大学理事会 | 抗b7-h6抗体、融合蛋白及其使用方法 |
| GB2508414A (en) * | 2012-11-30 | 2014-06-04 | Max Delbrueck Centrum | Tumour specific T cell receptors (TCRs) |
| EP2958938B1 (en) | 2013-02-20 | 2019-04-17 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized t-cell co-receptors |
| CA2900824A1 (en) * | 2013-02-22 | 2014-08-28 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized major histocompatibility complex |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| NL2013554B1 (en) | 2013-10-01 | 2016-01-08 | Kymab Ltd | Animal models and therapeutic molecules. |
| EP3067366A1 (en) * | 2015-03-13 | 2016-09-14 | Max-Delbrück-Centrum Für Molekulare Medizin | Combined T cell receptor gene therapy of cancer against MHC I and MHC II-restricted epitopes of the tumor antigen NY-ESO-1 |
| CN113349159B (zh) | 2015-04-06 | 2022-11-11 | 瑞泽恩制药公司 | 非人动物中的人源化t细胞介导的免疫应答 |
| MA44907A (fr) * | 2015-09-11 | 2018-07-18 | Agenus Inc | Cellules hôtes génétiquement modifiées et leurs procédés d'utilisation |
| JP7058223B2 (ja) | 2016-04-15 | 2022-04-21 | メモリアル スローン ケタリング キャンサー センター | トランスジェニックｔ細胞及びキメラ抗原受容体ｔ細胞組成物及び関連方法 |
| WO2018233608A1 (en) * | 2017-06-19 | 2018-12-27 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED TO CD28 HUMAN OR CHIMERIC |
| CN109136261B (zh) | 2017-06-19 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化cd28基因改造动物模型的制备方法及应用 |
| WO2020018715A1 (en) | 2018-07-17 | 2020-01-23 | Massachusetts Institute Of Technology | Soluble multimeric immunoglobulin-scaffold based fusion proteins and uses thereof |
| JP7422365B2 (ja) * | 2018-07-26 | 2024-01-26 | 国立大学法人京都大学 | 外来抗原レセプター遺伝子導入細胞の製造方法 |
| WO2023070126A1 (en) * | 2021-10-22 | 2023-04-27 | Regents Of The University Of Minnesota | Genetically engineered t cell receptors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5859312A (en) * | 1992-09-11 | 1999-01-12 | The Regents Of The University Of California | Transgenic non-human animals having targeting endogenous lymphocyte transduction genes and cognate human transgenes |
Family Cites Families (8)
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| US256591A (en) | 1882-04-18 | Adding-machine | ||
| US6150584A (en) * | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| EP1916300A1 (en) * | 1995-08-29 | 2008-04-30 | Kirin Pharma Kabushiki Kaisha | Chimeric animal and method for producing the same |
| WO1997032603A1 (en) * | 1996-03-05 | 1997-09-12 | The Scripps Research Institute | Recombinant constructs encoding t cell receptors specific for human hla-restricted tumor antigens |
| ES2301183T3 (es) * | 1996-12-03 | 2008-06-16 | Amgen Fremont Inc. | Anticuerpo completamente humano que se une al receptor del egfr. |
| DE19816129A1 (de) * | 1998-04-09 | 1999-10-14 | Dolores Schendel | T-Zellrezeptor-Expressionskassette |
| DE102010004180A1 (de) | 2010-01-07 | 2011-07-14 | KAUTEX TEXTRON GmbH & Co. KG, 53229 | Tropfenabscheider |
| US8943086B2 (en) | 2012-06-29 | 2015-01-27 | Sap Se | Model-based backend service adaptation of business objects |
-
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- 2001-12-19 JP JP2002559550A patent/JP2005505236A/ja active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5859312A (en) * | 1992-09-11 | 1999-01-12 | The Regents Of The University Of California | Transgenic non-human animals having targeting endogenous lymphocyte transduction genes and cognate human transgenes |
Non-Patent Citations (2)
| Title |
|---|
| International Immunology, 5(1), 1993, Rothe et. al., pg 11-17 * |
| Nature Genetics, 23, 1999, Masden et. al., pg 343-347 * |
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| US20030093818A1 (en) | 2003-05-15 |
| JP2009034106A (ja) | 2009-02-19 |
| WO2002059263A9 (en) | 2003-09-12 |
| CA2432133A1 (en) | 2002-08-01 |
| WO2002059263A2 (en) | 2002-08-01 |
| EP1409646A4 (en) | 2005-04-06 |
| EP1409646B1 (en) | 2012-06-13 |
| JP2005505236A (ja) | 2005-02-24 |
| ES2389251T3 (es) | 2012-10-24 |
| DK1409646T3 (da) | 2012-08-06 |
| WO2002059263A3 (en) | 2004-02-26 |
| EP1409646A2 (en) | 2004-04-21 |
| CA2432133C (en) | 2012-11-13 |
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